Rosanna Grossi

Human bocavirus infection in hospitalized children in Italy.

Background  Human bocavirus (HBoV) was first discovered in Sweden in 2005 and has now been found worldwide; however its role in clinically relevant diseases has not yet been clearly defined.

The role of terlipressin in the management of severe pulmonary hypertension in congenital diaphragmatic hernia.

SIR—Infants with congenital diaphragmatic hernia (CDH) are prone to develop profound hypoxemia related to lung hypoplasia and persistent pulmonary hypertension (PPH) despite optimized ventilatory management and selective pulmonary vasodilator drugs. Terlipressin (tricyl-lysinevasopressin), a long-acting vasopressin analogue, is a potent vasopressor drug that has been used to treat hypotension in various conditions, especially catecholamine-resistant shock (1). The case we report of a newborn infant with CDH in whom severe PPH refractory to inhaled NO (iNO) promptly responded to terlipressin draws attention to this drug as an effective alternative to treat hypoxemia associated with PPH when pulmonary vasodilators fail. A baby girl weighing 2.7 kg, with a left-sided diaphragmatic hernia and severe pulmonary hypoplasia confirmed by magnetic resonance imaging at 22 weeks gestation, was born at 38 weeks via cesarean section. The baby was intubated in the delivery room, sedated, and manually ventilated (Apgar scores 1¢:2; 5¢:5, 10¢:8). Despite aggressive mechanical ventilation settings, the baby remained poorly ventilated and oxygenated (oxygenation index=34, pCO2 = 11.9 kPa). High frequency oscillatory ventilation [HFOV; mean airway pressure (MAP) = 21 cmH2O, F = 13 Hz, DP = 70 cmH2O] reduced hypercapnia (pCO2 = 5.8 kPa) and improved oxygenation. At the same time, she was empirically started on 20 ppm iNO, and a single surfactant dose was administered. After the first 12 h of life, because oxygen requirements increased and hypercapnia developed, HFOV parameters were gradually adjusted (MAP = 28, F = 7 Hz, DP = 70 cmH2O), and iNO was increased to 34 ppm. Echocardiographic studies indicated right ventricular dysfunction and a bidirectional shunt through the ductus arteriosus with a pulmonary artery pressure (PAP) of 70 mmHg estimated on tricuspidal regurgitation, suggesting severe pulmonary hypertension. Inotropic agents at increasing doses (dobutamine up to 10 lgÆkgÆmin and dopamine up to 20 lgÆkgÆmin) and appropriate fluid therapy were given to increase the baby’s blood pressure that was measured by femoral artery catheterization. At 48 h of life, profound hypoxemia and hypotension (Figure 1) led to cardiac arrest. Adrenaline added to the inotropic regimen transiently improved circulatory failure. The baby’s condition nevertheless worsened again and despite therapy with fluids and frusemide marked oliguria (<0.5 mlÆkgÆh) developed, accompanied by hypotension and hypoxemia (pH=6.97, postductal pO2 = 4.9 kPa, pCO2 = 15.5 kPa, base excess = )8.4). After obtaining approval from the parents and hospital committee, as rescue therapy to reverse catecholamine-resistant shock, we used intravenous terlipressin (5 lgÆkg as a bolus) that simultaneously normalized systemic arterial pressure and improved oxygenation. Terlipressin infusion (5 lgÆkgÆh) was then maintained to keep the systemic blood pressure higher than the PAP. Echocardiographic examination showed a slight decrease in PAP (65 mmHg) and a reversed right-to-left shunt. Terlipressin induced no evident adverse effects such as ischemic tissue injury, intestinal ischemia, myocardial ischemia, or ventricular arrhythmias. On days 3–4, the baby’s renal function improved and increased oxygenation allowed HFOV parameters to be reduced (MAP from 28 to 20 cmH2O). Echocardiographic indices of pulmonary hypertension progressively improved from day 3 to day 6 (PAP 35 mmHg on day 5 of life). Terlipressin was weaned off on day 5 of life and suspended on day 6. At 8 days of age, the baby girl underwent surgery. On followup, the child appeared developmentally normal and thrived well. There are no previous reports describing the use of terlipressin in the management of pulmonary hypertension with or without circulatory shock in newborn infants. Our case thus represents the first instance of the use of terlipressin to relieve severe hypoxemia developing as a consequence of PPH and circulatory shock after failure of conventional treatments. In our case, severe hypotension prevented us from using any of the standard alternatives to iNO because they would have dilated the pulmonary circulation but further decreased systemic blood pressure (2). We therefore used a systemic vasopressor that increased the ratio of systemic blood pressure to pulmonary arterial 0 20 40 60 80 100 120

Upregulation of interferon-induced genes in infants with virus-associated acute bronchiolitis.

To determine whether there is an airway IFN response in infants with acute bronchiolitis and to establish whether the rate of such a response is related to the severity of illness, the expression of some IFN-induced genes was measured in nasopharyngeal washes from 39 infants with acute bronchiolitis. The results indicate that in infants with a virus-associated acute bronchiolitis there is a strong activation of IFN system and that the severity of illness is inversely related to the level of expression of IFN-induced genes. This suggests that the IFN response plays an important role in determining virus–associated respiratory disease in early life.To determine whether there is an airway IFN response in infants with acute bronchiolitis and to establish whether the rate of such a response is related to the severity of illness, the expression of some IFN-induced genes was measured in nasopharyngeal washes from 39 infants with acute bronchiolitis. The results indicate that in infants with a virus-associated acute bronchiolitis there is a strong activation of IFN system and that the severity of illness is inversely related to the level of expression of IFN-induced genes. This suggests that the IFN response plays an important role in determining virus-associated respiratory disease in early life.

A BRIEF COMMUNICATION

To determine whether there is an airway IFN response in infants with acute bronchiolitis and to establish whether the rate of such a response is related to the severity of illness, the expression of some IFN-induced genes was measured in nasopharyngeal washes from 39 infants with acute bronchiolitis. The results indicate that in infants with a virus-associated acute bronchiolitis there is a strong activation of IFN system and that the severity of illness is inversely related to the level of expression of IFN-induced genes. This suggests that the IFN response plays an important role in determining virus–associated respiratory disease in early life.To determine whether there is an airway IFN response in infants with acute bronchiolitis and to establish whether the rate of such a response is related to the severity of illness, the expression of some IFN-induced genes was measured in nasopharyngeal washes from 39 infants with acute bronchiolitis. The results indicate that in infants with a virus-associated acute bronchiolitis there is a strong activation of IFN system and that the severity of illness is inversely related to the level of expression of IFN-induced genes. This suggests that the IFN response plays an important role in determining virus-associated respiratory disease in early life.

Pharyngeal and esophageal pressure measurements to evaluate respiratory mechanics in infants on high flow nasal cannula: A feasibility study

High-flow humidified nasal cannula (HFNC) is often used to relieve respiratory distress in children with acute pulmonary disease, although its effects on respiratory mechanics have not been objectively studied. The purpose of this study was to test the feasibility of measuring pharyngeal (PP) and esophageal (Pes) pressures of young children on HFNC oxygen therapy through a specifically designed new monitoring, acquisition, and elaboration system (MAES). Through MAES we recorded and elaborated Pes and PP tracings obtained through esophageal and pharyngeal catheters in a group of young children hospitalized in a Pediatric Intensive Care Unit because of respiratory distress. All traces were recorded during spontaneous breathing and on HFNC 1 and 2 L/kg/min. To determine the onset and the end of inspiration, the Pes and PP signals were synchronized with the inspiratory flow obtained by a flow transducer placed in the HFNC circuit. Direct measurement of inspiratory flow by a face mask pneumotachograph also allowed for inspiratory tidal volume (TV) measurement which was used together with Pes curve to build Campbells diagram as well as the static lung and chest wall recoil curves required for pressure time product (PTP) evaluation. Using MAES we were able to obtain: time interval between the beginning of inspiratory effort and inspiration (Tdelay), TV, intrinsic positive end expiratory pressure (PEEPi), total inspiratory Pes variation (ΔPes), transpulmonary pressure at end of inspiration (Ptpei), dynamic lung compliance (CLdyn), total lung resistance (RLtot) along with all the relevant components of the inspiratory work of breathing (WOB) and PTP. We believe that this new system will allow clinicians for a bedside monitoring of respiratory distress in infants treated with HFNC and to modify flow rates accordingly.

Control of breathing

The control system of breathing can be considered as a closed loop system, consisting of two subsystems: the controlling system and the controlled system. Both systems are defined by their input-output relationships. The controlling system is defined by the Respiratory Centers that are responsible for two separate, but overlapping, patterns: the automatic control pattern and the behavioral or voluntary control. In the controlling system the input is the blood gas value and the output is some parameters of ventilation. The controlled system is characterized by an input of ventilation and an output of blood gas values. In this closed loop system breathing is normally regulated by two anatomically distinct but functionally integrated elements, referred to as the metabolic and behavioral respiratory control systems. The metabolic control is concerned with blood gas homeostasis and the voluntary control relates with activities such as phonation and singing that use the ventilatory apparatus for purposes other than gas exchange.

Hospital management of severe bronchopulmonary dysplasia

Despite early surfactant therapy, betterventilator strategies and greater use of noninvasive positive pressure ventilation, bronchopulmonary dysplasia (BPD)continues to be a complication of premature births. The mainstay of supportive care for infants with severe BPD is mechanical ventilation with an endotracheal tube, however treatmentcan last for a long time and have many complications. When safe extubation is not possible because of multiple failed attempts, tracheostomy is sometimes recommended [1-5]. In all age groups outside the neonatal period, placement of a tracheostomy is considered after a few weeks of mechanicalventilation [6,7]. By contrast, the optimum time and safety procedures have not yet been determined for the placement of a tracheostomy in infants with BPD who need protracted ventilation. Reasons for not performing a tracheostomy in these patientsinclude technical concerns associatedwith small patient size or the need for high ventilator settings. On the other hand the placement of a tracheostomy early in the course of severe BPD could have positive effects such as improved comfort, decreased need for sedation, lower systemic corticosteroid exposure, and enhanced nutrition and growth. Recent data [8] suggest that a reasonable approach is that chronically ventilated infants should be assessed at 3 months of age, that is around or shortly after 40 weeks corrected gestational age. If the respiratory support remains high and has been so for 2 months with no evidence of improvement and after multiple attempts to wean the baby off positive pressure ventilation, then infants should be considered for a tracheostomy placement. Another important point highlighted by this report is that tracheostomies should be considered a safe procedure even in infants on high pressures and high concentrations of supplemental oxygen. Other results [9] suggest a potential association between earlier (<120 days) tracheostomy and better neurodevelopmental outcomes. Actually, while an infant awaits a tracheostomy, the medical focus is often on strategies to allow weaning and limit ventilator-associated lung injury. Following a tracheostomy, the focus may shift to maximizing parent–child interaction and developmental improvement. Furthermore, after tracheostomy, there is often an opportunity to wean the baby off sedating medications, which are frequently associated with increased risk of neurodevelopmental impairment. In conclusion tracheostomy does not mitigate the significant risk for adverse neurodevelopment that is associated with the many complications of prematurity; however, if tracheostomy is to be performed, earlier surgery may allow opportunities for enhanced neurodevelopmental outcomes.

Lung development in the late preterm.

An increasing incidence of moderate-to-late prematurity is observed worldwide (6-7% of all births). Moderate-to-late prematurity is a cause of important mortality and morbidity, even when it is just a few weeks before term gestation [1]. Respiratory issues related to moderate prematurity include delayed neonatal transition to air breathing, respiratory distress resulting from delayed fluid clearance, surfactant deficiency, and pulmonary hypertension. There is increasing evidence to support the hypothesis that preterm delivery, even in the absence of any neonatal respiratory disease, may have adverse effects on subsequent lung growth and development, and that these alterations may persist during the early years of life. Premature birth interrupts normal in utero lung development and results in an early transition from the hypoxic intrauterine environment to a comparatively hyperoxic atmospheric environment [2]. Alveolar walls may be thicker, impairing optimal gas exchange. Colin et al. proposed that preterm birth leads to decreased parenchyma elasticity and subsequent airway tethering, a mechanism by which airway wall compliance keeps surrounding alveoli well opened [3]. The long-term significance of reduced airway function early in life has been emphasized in a longitudinal study involving a large group of non-selected infants who had participated in the Tucson Children’s Respiratory study [4]. In this study Stern et al. showed that infants whose pulmonary function was in the lowest quartile also had pulmonary function in the lowest quartile through the years of follow-up until early adulthood. These findings in a normal unselected population, suggest that the level of pulmonary function in early life tracks and changes little with growth. Several authors suggest that deficits in lung function during early life, especially if associated with lower respiratory illnesses, increase the risk of chronic obstructive pulmonary disease in late adult life [5-7]. Of particular importance in this context may be the role played by RSV, which affects most children during their first year of life. The risk of life-threatening RSV infection appears relevant up to a post-conceptional age of 44 weeks. Stein et al. reported that RSV lower respiratory tract illness during the first 3 years of life in a healthy birth cohort was associated with recurrent wheeze up to age 11 [8]. In conclusion altered lung development is a characteristic feature of the late preterm infants and its impact on neonatal and postnatal morbidity needs to be considered.